In a small phase III trial, the combination of ublituximab, a glycoengineered antiCD20 antibody, and ibrutinib (Imbruvica) out-performed ibrutinib alone, according to Jeff Sharman, MD, of Willamette Valley Cancer Institute in Springfield, Ore.

As well as increasing the proportion of patients who responded to treatment, the combination also increased the proportion of patients without detectable residual disease, Sharman reported in an oral session at the American Society of Clinical Oncology annual meeting.

The open-label GENUINE trial was intended to compare the two regimens in patients with relapsed or refractory CLL, Sharman said. To be eligible, patients had to have at least one of three high-risk genetic variants: 17pdel, 11qdel, or TP53mut.

They also had to have measurable disease, an ECOG performance status of 2 or lower, no history of CLL transformation, and no previous treatment with a Bruton's tyrosine kinase inhibitor like ibrutinib.

The study was intended originally to look at objective response rates (ORRs) and progression-free survival (PFS) as co-endpoints, Sharman said, but slow enrolment led to a redesign in which the progression endpoint was dropped.

The investigators randomly assigned 117 patients to get ibrutinib at 420 mg daily, with or without infusions of 900 mg of ublituximab, (on days 1, 8 and 15 of the first cycle; day one of the next five cycles, and every third cycle thereafter).

After 11.4 months of follow-up, he said, 15 patients in the combination arm and 26 in the ibrutinib arm had dropped out of the study for various reason, including two and five, respectively, because of adverse events.

Overall, the adverse event profiles were similar between the arms, Sharman said, with the exception of infusion reactions in the combination arm, which were reported by 54% of patients.

Also, seven patients in the combination arm and 11 patients in the ibrutinib arm were off the study because of progression or death, he said.

The independent review committee assessed outcomes -- the best overall response rate, complete response rate, and minimal residual disease (MRD)-negativity -- and found that among combination patients, the response rate was 78%, significantly better than the 45% seen in the ibrutinib patients.

Those rates included complete responses in 7% of combination patients but none among those taking ibrutinib. Also, 19% of combination patients demonstrated MRD-negativity, compared with 2% of those getting ibrutinib.

Patients in both arms developed lymphocytosis, but the peak was markedly higher in ibrutinib patients and the elevation in lymphocytes lasted longer, he reported.

The study demonstrates better ORRs for the combination than for ibrutinib alone, commented Jain Nitin, MD, of MD Anderson Cancer Center in Houston in a formal discussion of the paper.

But there is no difference yet in PFS and indeed, the study is no longer powered to detect such a difference, he noted.

On the other hand, he said, it's known that in high-risk patients ibrutinib usually only leads at best to partial responses; the combination did better on that score and also delivered some complete responses.

The combination also led to a quicker resolution of lymphocytosis, but the "clinical relevance ... remains to be determined," Nitin said, adding that "longer follow-up is required" to see if the promise of the combination holds up.

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